Publications by authors named "Leena-Maija Aaltonen"

65 Publications

HPV-Positive Status Is an Independent Factor Associated With Sinonasal Inverted Papilloma Recurrence.

Laryngoscope 2021 Oct 25. Epub 2021 Oct 25.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Objectives: The present study aimed to evaluate human papillomavirus (HPV) occurrence in sinonasal inverted papilloma (SNIP), and to assess factors associated with HPV positivity and SNIP recurrence.

Study Design: Prospective study.

Methods: We prospectively collected clinical data and fresh tissue specimens from 90 consecutive patients treated for SNIP at Helsinki University Hospital, between 2015 and 2019. Fourteen patients with recurrent SNIP underwent repeated tumor sampling. All tissue specimens were analyzed for the presence of HPV. Factors associated with SNIP recurrence and HPV positivity were assessed.

Results: Among 107 SNIP specimens, 14 (13.1%) were positive for low-risk HPV and 6 (5.6%) were positive for high-risk HPV. HPV positivity was associated with an increased risk of recurrence (P = .004). Smoking was significantly associated with HPV positivity in SNIP (P = .01), but a history of HPV-related diseases or patient sexual habits did not correlate with HPV positivity. The recurrence rate was lower among patients with SNIP that underwent an attachment-oriented resection, compared to patients treated without attachment-oriented resections (78.6% vs 25.8%, P < .001).

Conclusions: The risk of SNIP recurrence was highly associated with 1) HPV positivity and 2) surgery without an attachment-oriented resection. Oncogenic HPV was rare in SNIP.

Level Of Evidence: 3 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29910DOI Listing
October 2021

Finnish Version of the Eating Assessment Tool (F-EAT-10): A Valid and Reliable Patient-reported Outcome Measure for Dysphagia Evaluation.

Dysphagia 2021 Sep 13. Epub 2021 Sep 13.

Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, P.O. Box 263, FI-00029, Finland.

Our aim was to validate a Finnish version of the Eating Assessment Tool (F-EAT-10) for clinical use and to test its reliability and validity in a multicenter nationwide study. Normative data were acquired from 180 non-dysphagic participants (median age 57.0 years, 62.2% female). Dysphagia patients (n = 117, median age 69.7 years, 53.0% female) referred to fiberoptic endoscopic evaluation of swallowing (FEES) completed F-EAT-10 before the examination and after 2 weeks. Patients underwent the 100-ml water swallow test (WST) and FEES was evaluated using the following three scales: the Yale Pharyngeal Residue Severity Rating Scale, Penetration-Aspiration Scale, and the Dysphagia Outcome Severity Scale. An operative cohort of 19 patients (median age 75.8 years, 57.9% female) underwent an endoscopic operation on Zenker's diverticulum, tight cricopharyngeal muscle diagnosed in videofluorography, or both. Patients completed the F-EAT-10 preoperatively and 3 months postoperatively. The cut-off score for controls was < 3 (sensitivity 94.0%, specificity 96.1%) suggesting that ≥ 3 is abnormal. Re-questionnaires for test-retest reliability analysis were available from 92 FEES patients and 123 controls. The intraclass correlation coefficient was excellent for the total F-EAT-10 score (0.93, 95% confidence interval 0.91-0.95). Pearson correlation coefficients were strong (p < 0.001) for each of the questions and the total score. Internal consistency as assessed by Cronbach's alpha was excellent (0.95). Some correlations between findings in FEES and 100-ml WST with F-EAT-10 were observed. The change in subjective symptoms of operative patients paralleled the change in F-EAT-10. F-EAT-10 is a reliable, valid, and symptom-specific patient-reported outcome measure for assessing dysphagia among Finnish speakers.
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http://dx.doi.org/10.1007/s00455-021-10362-9DOI Listing
September 2021

T1 glottic laryngeal cancer: the role of routine follow-up visits in detecting local recurrence.

Eur Arch Otorhinolaryngol 2021 Dec 6;278(12):4863-4869. Epub 2021 Aug 6.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, 00029, Helsinki, Finland.

Purpose: We assessed the treatment outcome and the benefits of routine follow-up visits in T1 glottic laryngeal squamous cell carcinoma (LSCC).

Methods: Medical records of patients diagnosed with stage T1 glottic LSCC (N = 303) in five Finnish university hospitals between 2003 and 2015 were reviewed. Moreover, data from the Finnish Cancer Registry and the Population Register Center were collected.

Results: Of all 38 recurrences, 26 (68%) were detected during a routine follow-up visit, and over half (21 of 38, 55%) presented without new symptoms. Primary treatment method (surgery vs. radiotherapy) was not connected with 5-year disease-specific survival (DSS) or laryngeal preservation rate.

Conclusion: The majority of recurrences were detected on a routine follow-up visit, and local recurrences often presented without new symptoms. Routine post-treatment follow-up of T1 glottic LSCC seems beneficial.

Trial Registration: Trial registration number and date of registration HUS/356/2017 11.12.2017.
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http://dx.doi.org/10.1007/s00405-021-06983-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553688PMC
December 2021

Persistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of Infection.

mBio 2021 02 2;12(1). Epub 2021 Feb 2.

Department of Virology, University of Helsinki, Helsinki, Finland

Human bocavirus 1 (HBoV1), a nonenveloped single-stranded DNA parvovirus, causes mild to life-threatening respiratory tract infections, acute otitis media, and encephalitis in young children. HBoV1 often persists in nasopharyngeal secretions for months, hampering diagnosis. It has also been shown to persist in pediatric palatine and adenoid tonsils, which suggests that lymphoid organs are reservoirs for virus spread; however, the tissue site and host cells remain unknown. Our aim was to determine, in healthy nonviremic children with preexisting HBoV1 immunity, the adenotonsillar persistence site(s), host cell types, and virus activity. We discovered that HBoV1 DNA persists in lymphoid germinal centers (GCs), but not in the corresponding tonsillar epithelium, and that the cell types harboring the virus are mainly naive, activated, and memory B cells and monocytes. Both viral DNA strands and both sides of the genome were detected, as well as infrequent mRNA. Moreover, we showed, in B-cell and monocyte cultures and tonsillar B cells, that the cellular uptake of HBoV1 occurs via the Fc receptor (FcγRII) through antibody-dependent enhancement (ADE). This resulted in viral mRNA transcription, known to occur exclusively from double-stranded DNA in the nucleus, however, with no detectable productive replication. Confocal imaging with fluorescent virus-like particles moreover disclosed endocytosis. To which extent the active HBoV1 GC persistence has a role in chronic inflammation or B-cell maturation disturbances, and whether the virus can be reactivated, will be interesting topics for forthcoming studies. Human bocavirus 1 (HBoV1), a common pediatric respiratory pathogen, can persist in airway secretions for months hampering diagnosis. It also persists in tonsils, providing potential reservoirs for airway shedding, with the exact location, host cell types, and virus activity unknown. Our study provides new insights into tonsillar HBoV1 persistence. We observed HBoV1 persistence exclusively in germinal centers where immune maturation occurs, and the main host cells were B cells and monocytes. In cultured cell lines and primary tonsillar B cells, we showed the virus uptake to be significantly enhanced by HBoV1-specific antibodies, mediated by the cellular IgG receptor, leading to viral mRNA synthesis, but without detectable productive replication. Possible implications of such active viral persistence could be tonsillar inflammation, disturbances in immune maturation, reactivation, or cell death with release of virus DNA, explaining the long-lasting HBoV1 airway shedding.
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http://dx.doi.org/10.1128/mBio.03132-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858059PMC
February 2021

European white paper: oropharyngeal dysphagia in head and neck cancer.

Eur Arch Otorhinolaryngol 2021 Feb 19;278(2):577-616. Epub 2020 Dec 19.

Head and Neck Oncology Service, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, TO, Italy.

Purpose: To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe.

Methods: Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion.

Results: Twenty-four sections on HNC-specific OD topics.

Conclusion: This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.
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http://dx.doi.org/10.1007/s00405-020-06507-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826315PMC
February 2021

Analysis of weekend effect on mortality by medical specialty in Helsinki University Hospital over a 14-year period.

Health Policy 2020 11 31;124(11):1209-1216. Epub 2020 Jul 31.

Diagnostic Center, Helsinki University Hospital and University of Helsinki, P.O. Box 720, 00029 HUS, Helsinki, Finland. Electronic address:

Background: The weekend effect, the phenomenon of patients admitted at the weekend having a higher mortality risk, has been widely investigated and documented in both elective and emergency patients. Research on the issue is scarce in Europe, with the exception of the United Kingdom. We examined the situation in Helsinki University Hospital over a 14-year period from a specialty-specific approach.

Materials And Methods: We collected the data for all patient visits for 2000-2013, selecting patients with in-hospital care in the university hospital and extracting patients that died during their hospital stay or within 30 days of discharge. These patients were categorized according to urgency of care and specialty.

Results: A total of 1,542,230 in-patients (853,268 emergency patients) met the study criteria, with 47,122 deaths in-hospital or within 30 days of discharge. Of 12 specialties, we found a statistically significant weekend effect for in-hospital mortality in 7 specialties (emergency admissions) and 4 specialties (elective admissions); for 30-day post-discharge mortality in 1 specialty (emergency admissions) and 2 specialties (elective admissions). Surgery, internal medicine, neurology, and gynecology and obstetrics were most sensitive to the weekend effect.

Conclusions: The study confirms a weekend effect for both elective and emergency admissions in most specialties. Reducing the number of weekend elective procedures may be necessary. More disease-specific research is needed to find the diagnoses most susceptible.
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http://dx.doi.org/10.1016/j.healthpol.2020.07.010DOI Listing
November 2020

Root causes of extended length of stay and unplanned readmissions after orthopedic surgery and hand surgery: a retrospective observational cohort study.

Patient Saf Surg 2020 26;14:27. Epub 2020 Jun 26.

Diagnostic Center, Hospital District of Helsinki and Uusimaa and University of Helsinki, Helsinki, Finland.

Background: While previous studies have evaluated the effect of some patient characteristics (e.g. gender, American Society of Anesthesiologists (ASA) class and comorbidity) on outcome in orthopedic and hand day surgery, more detailed information on anesthesia related factors has previously been lacking. Our goal was to investigate the perioperative factors that affect overstay, readmission and contact after day surgery in order to find certain patient profiles more prone to problemed outcomes after day surgery.

Methods: We examined orthopedic and hand day surgery at an orthopedic day surgery unit of Helsinki University Hospital. Patient data of all adult orthopedic and hand day surgery patients ( = 542) over a 3-month period (January 1 - March 31, 2015) operated on at the unit were collected retrospectively using the hospital's surgery database. These data comprised anesthesia and patient records with a follow-up period of 30 days post-operation. Patients under the age of 16 and patients not eligible for day surgery were excluded. Patient records were searched for an outcome of overstay, readmission or contact with the emergency room or policlinic. Pearson chi-square test, Fischer's exact test and multivariable logistic regression were used to analyze the effect of various perioperative factors on postoperative outcome.

Results: Various patient and anesthesia related factors were examined for their significance in the outcomes of overstay, readmission or contact. Female gender ( = 0.043), total amount of fentanyl ( = 0.00), use of remifentanil ( = 0.036), other pain medication during procedure ( = 0.005) and administration of antiemetic medication ( = 0.048) emerged as statistically significant on outcome after day surgery.

Conclusions: Overstay and readmission in orthopedic and hand day surgery were clearly connected with female patients undergoing general anesthesia and needing larger amounts of intraoperative opioids. By favoring local and regional anesthesia, side effects of general anesthesia, as well as recovery time, will decrease.
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http://dx.doi.org/10.1186/s13037-020-00249-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320581PMC
June 2020

Weekend effect on mortality by medical specialty in six secondary hospitals in the Helsinki metropolitan area over a 14-year period.

BMC Health Serv Res 2020 Apr 17;20(1):323. Epub 2020 Apr 17.

Diagnostic Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Background: The weekend effect is the phenomenon of a patient's day of admission affecting their risk for mortality. Our study reviews the situation at six secondary hospitals in the greater Helsinki area over a 14-year period by specialty, in order to examine the effect of centralization of services on the weekend effect.

Methods: Of the 28,591,840 patient visits from the years 2000-2013 in our hospital district, we extracted in-patients treated only in secondary hospitals who died during their hospital stay or within 30 days of discharge. We categorized patients based on the type of each admission, namely elective versus emergency, and according to the specialty of their clinical service provider and main diagnosis.

Results: A total of 456,676 in-patients (292,399 emergency in-patients) were included in the study, with 17,231 deaths in-hospital or within 30 days of discharge. A statistically significant weekend effect was observed for in-hospital and 30-day post-discharge mortality among emergency patients for 1 of 7 specialties. For elective patients, a statistically significant weekend effect was visible in in-hospital mortality for 4 of 8 specialties and in 30-day post-discharge mortality for 3 of 8 specialties. Surgery, internal medicine, and gynecology and obstetrics were most susceptible to this phenomenon.

Conclusions: A weekend effect was present for the majority of specialties for elective patients, indicating a need for guidelines for these admissions. More disease-specific research is necessary to find the diagnoses, which suffer most from the weekend effect and adjust staffing accordingly.
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http://dx.doi.org/10.1186/s12913-020-05142-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164185PMC
April 2020

Peritonsillar abscess may not always be a complication of acute tonsillitis: A prospective cohort study.

PLoS One 2020 3;15(4):e0228122. Epub 2020 Apr 3.

Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland.

The present study aimed to specify diagnostics for peritonsillar abscesses (PTAs) and to clarify the role of minor salivary glands. This prospective cohort study included 112 patients with acute tonsillitis (AT) and PTA recruited at a tertiary hospital emergency department between February and October 2017. All patients completed a questionnaire concerning their current disease. Serum amylase (S-Amyl) and C-reactive protein (S-CRP) levels, tonsillar findings, and pus aspirate samples and throat cultures were analyzed. Eight of 58 PTA patients (13.8%) had no signs of tonsillar infection. The absence of tonsillar erythema and exudate was associated with low S-CRP (p<0.001) and older age (p<0.001). We also observed an inverse correlation between S-Amyl and S-CRP levels (AT, r = -0.519; PTA, r = -0.353). Therefore, we observed a group of PTA patients without signs of tonsillar infection who had significantly lower S-CRP levels than other PTA patients. These findings support that PTA may be caused by an etiology other than AT. Variations in the S-Amyl levels and a negative correlation between S-Amyl and S-CRP levels may indicate that minor salivary glands are involved in PTA development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228122PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122714PMC
July 2020

Overstay and Readmission in Ear, Nose, and Throat Day Surgery-Factors Affecting Postanesthesia Course.

Ear Nose Throat J 2021 Aug 3;100(7):477-482. Epub 2019 Oct 3.

Department of Otorhinolaryngology-Head and Neck Surgery, 89593University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Aims: Many procedures in ear, nose, and throat (ENT) day surgery are carried out under local anesthesia in Finland, whereas many other countries use general anesthesia. We investigated overstay and readmission rates in local and general anesthesia at Helsinki University Hospital.

Material And Methods: We conducted a retrospective study on ENT (n = 1011) day surgery patients within a 3-month period using the hospital's surgery database to collect data pertaining to anesthesia, overstays, readmissions, and contacts within 30 days of surgery.

Objectives: We examined the effect of American Society of Anesthesiologists (ASA) class, age, sex, type of procedure, and anesthesia type on overstay, contact, and readmission rates.

Results: A multivariable logistic regression model included ASA class, age, sex, type of procedure, and anesthesia (local vs general). Sex, age, and type of procedure had an effect on the outcomes of overstay, readmission, or contact. With general anesthesia, 3.2% (n = 23) had an overstay or readmission compared to 1.4% (n = 4) after local anesthesia. This was mainly explained by the number of study outcomes in tonsillar surgery that was performed only in general anesthesia.

Conclusions: Day surgery could be done safely using local anesthesia, as the number of study outcomes was no greater than in general anesthesia. Sex, type of procedure, and age affected the rate of study outcomes, but ASA class and anesthesia form did not. Our overstay, contact, and readmission rates are on the same level, or lower, than in international studies.
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http://dx.doi.org/10.1177/0145561319872165DOI Listing
August 2021

Patient injuries in pediatric otorhinolaryngology.

Int J Pediatr Otorhinolaryngol 2019 May 3;120:36-39. Epub 2019 Feb 3.

Department of Vascular Surgery, Turku University Hospital and University of Turku, Turku, Finland.

Objectives: Patient injuries in children can have lifelong effects on the patient and a marked impact on the whole family. The aim of this study was to identify the errors and incidents leading to patient injuries in pediatric otorhinolaryngology (ORL) by evaluating accepted patient injury claims.

Methods: The records of all accepted patient injury claims in ORL between 2001 and 2011 were searched from the nationwide Patient Insurance Centre registry. Pediatric injuries were reviewed and evaluated in detail, and factors contributing to injury were identified.

Results: In the 10-year study period, 17 (7.6%) of the 223 patient injuries occurred in children, and of these, 15 (88%) were considered operative care. The median age of the patients was 8 years (range 3-16 years). All operations were performed as daytime elective surgery and by a fully trained specialist in 93% of the cases. One-half of the cases were routine surgeries for common ORL diseases. The most common incidences were incomplete surgery, retained gauze or foreign body, injury to adjacent anatomic structure, and insufficient charts or instructions (each occurred in 3 cases). The most frequent consequence was burn (n = 4). One child died because of post-tonsillectomy hemorrhage.

Conclusions: Patient injuries in pediatric ORL are strongly related to surgery. Most injuries occurred after routine operations by a fully trained specialist. Clinicians should be aware of the most likely scenarios resulting in claims.
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http://dx.doi.org/10.1016/j.ijporl.2019.02.007DOI Listing
May 2019

Serum matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1: Potential markers for malignant transformation of recurrent respiratory papillomatosis and for prognosis of laryngeal cancer.

Head Neck 2019 02 14;41(2):309-314. Epub 2018 Dec 14.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Biomarkers that could predict malignant transformation of recurrent respiratory papillomatosis (RRP) would be useful in patient follow-up. We investigated whether serum matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of metalloproteinase 1 (TIMP-1) could predict malignant transformation of RRP and whether they associate with survival in laryngeal squamous cell carcinoma (LSCC) without preexisting RRP.

Methods: We analyzed serum MMP-8 (S-MMP-8) and serum TIMP-1 (s-TIMP-1) in 114 patients: 55 were treated for RRP and 59 for LSCC without preexisting RRP. Five patients with RRP developed LSCC during follow-up.

Results: Elevated S-MMP-8 level in RRP was associated with malignant transformation (P = .01). Compared to patients with RRP, S-MMP-8 in patients with LSCC was significantly higher (P < .001). Increased S-TIMP-1 level in LSCC was associated with poor overall survival (P = .02) and recurrence-free survival (P = .05).

Conclusion: In RRP, high S-MMP-8 may predict malignant transformation. In LSCC, elevated S-TIMP-1 is connected to poor survival.
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http://dx.doi.org/10.1002/hed.25459DOI Listing
February 2019

Authors' response to Commentary on "Role of barium swallow pharyngoesophagography in the management of globus pharyngeus".

Eur Arch Otorhinolaryngol 2018 12 21;275(12):3095-3096. Epub 2018 Sep 21.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, 00029, Helsinki, Finland.

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http://dx.doi.org/10.1007/s00405-018-5133-yDOI Listing
December 2018

Globus pharyngeus: a review of etiology, diagnostics, and treatment.

Eur Arch Otorhinolaryngol 2018 Aug 25;275(8):1945-1953. Epub 2018 Jun 25.

Department of Otorhinolaryngology, Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Globus is a non-painful sensation of a lump or a foreign body in the throat, and it frequently improves with eating. Although globus is a common symptom, only little is known about the etiology, and the causes have remained controversial. Previously, globus was labelled as a hysterical symptom. However, nowadays, the research has been mainly focused on somatic causes and it is suspected that the etiology is complex. Because of the unclear etiology, the diagnostics and treatment are varying, predisposing patients to possible unnecessary investigations. This review presents the current literature of globus: its etiology, diagnostics, and treatment. In addition, a special aim is to discuss the rational investigation methods in globus diagnostics and present a diagnostic algorithm based on recent researches.
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http://dx.doi.org/10.1007/s00405-018-5041-1DOI Listing
August 2018

Symptom relief and health-related quality of life in globus patients: a prospective study.

Logoped Phoniatr Vocol 2019 Jul 9;44(2):67-72. Epub 2017 Nov 9.

a Department of Otorhinolaryngology - Head and Neck Surgery , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.

Globus may be a persistent symptom impairing patients' quality of life. Diagnostics and treatment are controversial but some globus patients may benefit from reassurance and attention. We investigated how globus symptoms change during a short-term follow-up without any treatment after an examination by an ear, nose and throat (ENT) physician and further diagnostic procedures. We also surveyed whether patients with persistent globus suffer from simultaneous voice problems. The study comprised 30 consecutive globus patients referred to Helsinki University Hospital, Department of Otorhinolaryngology - Head and Neck Surgery. We performed an ENT examination and scored patients' videolaryngostroboscopies using the Reflux Finding Score (RFS). Patients filled in three questionnaires: the Reflux Symptom Index (RSI), the Deglutition Handicap Index (DHI) and the 15-Dimensional Measure of Health-Related Quality of Life (15-D HRQoL). Patients underwent transnasal esophagoscopy, high-resolution manometry, and 24-hour multichannel intraluminal impedance and pH monitoring. After a four-month follow-up, patients re-answered the same questionnaires and a speech and language pathologist (SLP) examined the patients. Baseline and follow-up questionnaires were available from 27 (90%) patients. According to the RSI (p = .001) and the DHI (p = .003), patients' symptoms diminished after four months. The 15-D showed improvement in one subscale measuring discomfort and symptoms (p = .023). The SLP examined 23 (77%) patients, finding functional voice problems in six (26%). The study showed that most globus patients felt their symptoms diminished without any treatment during four months. In some patients, coexisting voice problems may be associated with persistent globus.
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http://dx.doi.org/10.1080/14015439.2017.1397741DOI Listing
July 2019

Prevalence of high-risk human papillomavirus infection and cancer gene mutations in nonmalignant tonsils.

Oral Oncol 2017 10 18;73:77-82. Epub 2017 Aug 18.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, 00130 Helsinki, Finland.

Objectives: To analyze the prevalence of high-risk HPV (human papillomavirus) and genetic alterations in nonmalignant tonsils.

Methods: We collected benign fresh tonsillar tissue specimens from 477 patients undergoing tonsillectomy because of chronic tonsillitis or tonsillar hypertrophy in 2012 (Group A, n=237) and in 2015 (Group B, n=240). Luminex xMAP technique served to detect E6/E7 DNA from 16 different high-risk HPV types. Tonsillar DNA and peripheral blood leukocyte DNA from the infected individuals were analyzed using Nimblegen SeqCap EZ Comprehensive Cancer Design panel. The panel targets 578 different genes that are relevant in carcinogenesis. HPV negative tonsillar specimens from age- and gender matched individuals were used as controls. All specimens harboring high-risk HPV were analyzed using fluorescence in situ hybridization (FISH).

Results: Five of 477 (1.0%) patients tested positive for the following HPV types: HPV16 (two cases), HPV52 (one case), HPV66 (one case), HPV52 and HPV68 (coinfection, one case). FISH analyses showed that the appearance of HPV in specimens infected with HPV 16 was episomal. Benign tonsils infected with high-risk HPV harbored mutations in EP300, NF1, PIK3CA, and RB1 which are considered relevant in the development of HPV-associated head and neck squamous cell carcinoma (SCC).

Conclusions: The prevalence of high-risk HPV in nonmalignant tonsils is low. High-risk HPV positive tonsils harbored mutations in genes that are commonly altered in HPV-associated head and neck SCC. The role of these mutations in tonsillar carcinogenesis is an interesting target for future research.
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http://dx.doi.org/10.1016/j.oraloncology.2017.08.010DOI Listing
October 2017

Iatrogenic patient injuries in otology during a 10-year period: review of national patient insurance charts.

Acta Otolaryngol 2018 Jan 14;138(1):16-20. Epub 2017 Sep 14.

b Department of Otorhinolaryngology - Head and Neck Surgery , Helsinki University Hospital and University of Helsinki , Helsinki , Finland.

Objective: To assess patient injury characteristics and contributing factors in otology.

Methods: Data on the accepted patient-injury claims involving otorhinolaryngology (ORL), closed between 2001 and 2011, from the Finnish Patient Insurance Centre registry was retrieved. We included all injuries concerning otology, with evaluation and classification of their causes and types.

Results: During the 10-year study period, a total of 44 claims were accepted as compensated patient injuries in otology. From a total of 233 patient injuries in all ORL, this amounted to 19%. In outpatient care, occurred 12 (27%) injuries and in surgical procedures 32 (73%). Five (11%) patients were children. Errors in surgical technique were identified as the primary cause of the injury in 22 (69%) operation-related cases. Failure to remove all auricular tampons or packing in postoperative control was a contributing factor in 4 (13%) injuries, a facial nerve was damaged in 9 (28%) operations, and in 12 (38%) patients, the injury resulted in severe hearing loss or deafness. Six patients (21%) needed one or more re-operations related to the injury, of which two were due to an incomplete primary operation.

Conclusion: Typical compensated patient injuries in operative otology resulted from common complications of common operations in high volume centres.
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http://dx.doi.org/10.1080/00016489.2017.1375153DOI Listing
January 2018

The presence of minor salivary glands in the peritonsillar space.

Eur Arch Otorhinolaryngol 2017 Nov 12;274(11):3997-4001. Epub 2017 Sep 12.

Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland.

Peritonsillar abscess (PTA) is traditionally considered only a purulent complication of acute tonsillitis (AT), but may be related to infection of minor salivary glands. We analysed the presence of peritonsillar minor salivary glands and inflammation patterns in 114 adult tonsils representing three patient groups: recurrent AT, chronic tonsillitis (CT), and PTA. Samples acquired from elective tonsillectomies were stored in formalin, and after preparation were microscopically examined for inflammation and fibrotic changes. Clinical features and histological characteristics were compared between the groups. Of all tonsils, the minor salivary glands were present in 77 (67.5%). Glands located near the tonsillar tissue showed signs of infection in 73 (94.8%), while only 3 (15.0%) of 20 glands located deeper in the peritonsillar space were infected. Compared to patients with recurrent AT and CT, those with PTA more often presented with periductal inflammation, p < 0.011 (PTA 82.1%, AT 42.9%, and CT 63.6%). The majority of our 114 tonsillectomy specimens, collected from patients with AT, CT, or PTA, presented with infected minor salivary glands, and inflammation of the peritonsillar space glands was evident. To further elucidate the association between these glands and PTA, tonsillar samples should be collected and analysed from patients during the acute phase of infection.
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http://dx.doi.org/10.1007/s00405-017-4738-xDOI Listing
November 2017

Multiplex detection in tonsillar tissue of all known human polyomaviruses.

BMC Infect Dis 2017 06 8;17(1):409. Epub 2017 Jun 8.

Virology, University of Helsinki, Helsinki, Finland.

Background: In the past few years, eleven new human viruses have joined the two previously known members JCPyV and BKPyV of the Polyomaviridae family, by virtue of molecular methods. Serology data suggest that infections with human polyomaviruses (HPyVs) occur since childhood and the viruses are widespread in the general population. However, the viral persistence sites and transmission routes are by and large unknown. Our previous studies demonstrated that the four new HPyVs - KIPyV, WUPyV, MCPyV and TSPyV - were present in the tonsils, and suggested lymphoid tissue as a persistent site of these emerging human viruses. We developed a Luminex-based multiplex assay for simultaneous detection of all 13 HPyVs known, and explored their occurrence in tonsillar tissues of children and adults mostly with tonsillitis or tonsillar hypertrophy.

Methods: We set up and validated a new Luminex-based multiplex assay by using primer pairs and probes targeting the respective HPyV viral protein 1 (VP1) genes. With this assay we tested 78 tonsillar tissues for DNAs of 13 HPyVs.

Results: The multiplex assay allowed for simultaneous detection of 13 HPyVs with high analytical sensitivity and specificity, with detection limits of 10-10 copies per microliter, and identified correctly all 13 target sequences with no cross reactions. HPyV DNA altogether was found in 14 (17.9%) of 78 tonsils. The most prevalent HPyVs were HPyV6 (7.7%), TSPyV (3.8%) and WUPyV (3.8%). Mixed infection of two HPyVs occurred in one sample.

Conclusions: The Luminex-based HPyV multiplex assay appears highly suitable for clinical diagnostic purposes and large-scale epidemiological studies. Additional evidence was acquired that the lymphoid system plays a role in HPyV infection and persistence. Thereby, shedding from this site during reactivation might take part in transmission of the newly found HPyVs.
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http://dx.doi.org/10.1186/s12879-017-2479-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465560PMC
June 2017

Extinct type of human parvovirus B19 persists in tonsillar B cells.

Nat Commun 2017 04 4;8:14930. Epub 2017 Apr 4.

Department of Virology, University of Helsinki, Helsinki 00290, Finland.

Parvovirus B19 (B19V) DNA persists lifelong in human tissues, but the cell type harbouring it remains unclear. We here explore B19V DNA distribution in B, T and monocyte cell lineages of recently excised tonsillar tissues from 77 individuals with an age range of 2-69 years. We show that B19V DNA is most frequent and abundant among B cells, and within them we find a B19V genotype that vanished from circulation >40 years ago. Since re-infection or re-activation are unlikely with this virus type, this finding supports the maintenance of pathogen-specific humoral immune responses as a consequence of B-cell long-term survival rather than continuous replenishment of the memory pool. Moreover, we demonstrate the mechanism of B19V internalization to be antibody dependent in two B-cell lines as well as in ex vivo isolated tonsillar B cells. This study provides direct evidence for a cell type accountable for B19V DNA tissue persistence.
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http://dx.doi.org/10.1038/ncomms14930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382274PMC
April 2017

The feasibility of NBI in patients with suspected upper airway lesions: A multicenter study.

Laryngoscope 2017 08 22;127(8):1821-1825. Epub 2017 Feb 22.

Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Hospital, Turku.

Objective: Narrow band imaging (NBI) improves diagnosis of laryngopharyngeal cancer, but most reported NBI studies are from experienced centers. Feasibility reports on use at everyday outpatient departments are needed.

Study Design: Researcher-initiated, prospective, multicenter.

Methods: Participating physicians were instructed in NBI technique during a 4-hour meeting. Patients underwent an examination that included endoscopy with white light (WL) high-definition (HD) TV and NBI filter in the selected time period. All suspicious lesions were biopsied. The medical records of patients with NBI negative findings were evaluated 6 months after the visit to detect all possible malignant lesions coming into view at mucosal sites. These were considered as false-negative cases, enabling long-term assess to the positive predictive value (NPV) of the protocol.

Results: We enrolled 125 patients. Of those, 84 (67.2%) were males and the median age was 65 years (range, 35-91). In analysis of the accuracy of WL HD TV and NBI against biopsy, the sensitivity and specificity of WL HD TV were 62% and 81%, respectively; and the sensitivity and specificity of NBI were 100% and 84%, respectively. The diagnostic accuracy of NBI was significantly better (P < 0.05). When analyzing medical records 6 months after the initial examination, we found three patients who had been diagnosed with a malignant lesion (NPV of NBI of 96.8%).

Conclusion: Narrow band imaging is readily implemented in an everyday outpatient practice, and there seems to be better detection rates of dysplastic/carcinoma lesions with HD NBI compared to HD WL.

Level Of Evidence: 2b. Laryngoscope, 127:1821-1825, 2017.
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http://dx.doi.org/10.1002/lary.26526DOI Listing
August 2017

Quality of life of patients with recurrent respiratory papillomatosis.

Laryngoscope 2017 08 15;127(8):1826-1831. Epub 2016 Nov 15.

Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Objectives/hypothesis: Recurrent respiratory papillomatosis (RRP) is a disease with a high disease burden. Few studies have assessed quality of life (QoL) of RRP patients. This study compares QoL of these patients with controls. Associations between QoL and sociodemographic and illness-related factors are examined, as is uptake of psychosocial care and speech therapy.

Study Design: Prospective cross-sectional questionnaire research.

Methods: Ninety-one RRP patients (response = 67%) from two university hospitals in the Netherlands and Finland completed the following patient reported outcome measures: (HADS), 15-dimensional health-related quality-of-life scale (15D), Voice Handicap Index (VHI) and the RAND 36-item health-related quality-of-life survey instrument (RAND-36) assessing health-related QoL and voice handicap, and they provided sociodemographic, illness-related, and allied healthcare use. Descriptive analyses, χ tests, t tests, analysis of variance tests, and Pearson correlations were computed to describe the study population and to examine differences between groups.

Results: RRP patients had significantly higher mean scores on depression, health-related QoL (15D) and on voice problems (VHI), and significantly lower mean scores on anxiety than controls. Dutch patients had more pain and a decreased general health perception (RAND-36) than controls. Dutch patients and older patients were more depressed, women were more anxious, older patients had lower health-related QoL, and smoking was significantly associated with voice handicap. Patients who had received psychosocial care had significantly higher HADS-depression mean scores than patients who did not receive psychosocial care.

Conclusions: Having RRP has significant effect on voice-related QoL and depression, but has no negative effect on anxiety and health-related QoL. Risk factors for decreased functioning are different than previously hypothesized by many authors. Prevention should be aimed at these risk factors.

Level Of Evidence: 4. Laryngoscope, 127:1826-1831, 2017.
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http://dx.doi.org/10.1002/lary.26413DOI Listing
August 2017

Systemic matrix metalloproteinase-8 response in chronic tonsillitis.

Infect Dis (Lond) 2017 Apr 2;49(4):302-307. Epub 2016 Nov 2.

a Department of Otorhinolaryngology - Head and Neck Surgery , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.

The development of several life-long diseases, such as coronary heart disease, is affected by low-grade systemic inflammation. Data on the potential long-term health effects of chronic tonsillitis are limited. Many inflammatory conditions present with enhanced systemic matrix metalloproteinase (MMP)-8 response. In head and neck cancer, high plasma level of tissue inhibitor of metalloproteinase (TIMP)-1 predicts poor prognosis. We analyzed S-MMP-8 with immunofluorometric assay and S-TIMP-1 with an immunosorbent assay in 175 consecutive patients undergoing tonsillectomy for benign tonsillar disease, and in 33 control patients with tonsillar squamous cell carcinoma. Tonsillar human papillomavirus (HPV) status was determined by PCR. In patients with benign tonsillar disease, chronic tonsillitis without hypertrophy was associated with enhanced systemic MMP-8 response. Compared to patients with benign tonsillar disease, patients with tonsillar squamous cell carcinoma had significantly higher concentrations of S-MMP-8 and S-TIMP-1. Neither S-MMP-8 nor S-TIMP-1 correlated with tonsillar HPV positivity.
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http://dx.doi.org/10.1080/23744235.2016.1248484DOI Listing
April 2017

Work-up of globus: assessing the benefits of neck ultrasound and videofluorography.

Eur Arch Otorhinolaryngol 2017 Feb 17;274(2):931-937. Epub 2016 Sep 17.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, FI-00029 HUS, Helsinki, Finland.

Globus patients with normal ear, nose, and throat (ENT) status are a diagnostic challenge. The symptom may be long lasting and cause concern about malignancy, leading to possibly unnecessary further investigation. The aim of the study was to assess whether radiological examinations are useful in globus diagnostics, how often patients suffer from persistent globus, and whether globus patients with normal ENT status develop a malignancy during a follow-up. We reviewed medical records of all 76 globus patients referred to Helsinki University Hospital, Department of Otorhinolaryngology-Head and Neck Surgery in 2009. Patient history and findings in physical and radiological examinations were registered. A questionnaire concerning patients' present pharyngeal symptoms was sent 3 and 6 years after their initial visit. Data from the Finnish Cancer Registry revealed whether patients developed malignancies within a 3-year follow-up. Based on medical records, neck ultrasound was performed for 37 (49 %) and videofluorography for 22 patients (29 %), with nonsignificant findings. After a 3- and 6-year follow-up, half patients indicated that they were asymptomatic or had fewer symptoms, whereas the rest had persistent symptoms. The Finnish Cancer Registry data confirmed that globus patients developed no head and neck malignancies during a 3-year follow-up. In the present study, neck ultrasound and videofluorography showed no additional benefit to evaluate the globus etiology in patients whose ENT status was normal. Half the globus patients suffered from persistent symptoms after a 3- and 6-year follow-up, indicating that globus may cause discomfort chronically. However, no patients developed malignancies during a 3-year follow-up.
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http://dx.doi.org/10.1007/s00405-016-4307-8DOI Listing
February 2017

Validation of the Distress Thermometer and Problem List in Patients with Recurrent Respiratory Papillomatosis.

Otolaryngol Head Neck Surg 2017 01 3;156(1):180-188. Epub 2016 Oct 3.

1 Department of Otorhinolaryngology-Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Objective There is no specific clinical tool for physicians to detect psychosocial and physical distress or health care need in patients with recurrent respiratory papillomatosis (RRP). The main aim of this study is to validate the RRP-adapted Distress Thermometer and Problem List (DT&PL). Study Design Prospective cross-sectional questionnaire research. Setting Academic tertiary care medical centers in Groningen, Netherlands, and Helsinki, Finland. Subjects and Methods Ninety-one juvenile- and adult-onset RRP patients participated from the departments of otorhinolaryngology-head and neck surgery of the University Medical Center Groningen, Netherlands, and Helsinki University Hospital, Finland. The Hospital Anxiety and Depression Scale was used as the gold standard. Results A DT cutoff score ≥4 gave the best sensitivity and specificity. Thirty-one percent of patients had significant distress according to the DT cutoff. Significantly more patients with a score above than under the cutoff had a referral wish. The PL appeared to be reliable. Patients' opinions on the DT&PL were largely favorable. Conclusion The Dutch and Finnish versions of the DT&PL are valid, reliable screening tools for distress in RRP patients.
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http://dx.doi.org/10.1177/0194599816668307DOI Listing
January 2017

Dysphagia and malignancy: A three-year follow-up and survey of National Cancer Registry data.

Laryngoscope 2016 09 21;126(9):2073-8. Epub 2015 Dec 21.

Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University and Helsinki University Hospital, Helsinki, Finland.

Objectives/hypothesis: Dysphagia may cause concern about malignancy. Symptoms are often unspecific; thus, it is essential to identify those requiring further investigations.

Study Design: Retrospective study combined with patient survey.

Methods: Case records of the 303 dysphagia patients referred in 2009 to Helsinki University Hospital, Department of Otorhinolaryngology-Head and Neck Surgery were surveyed. Based on clinical data, the main cause of symptoms divided patients into five groups. Alarming signs were food sticking in the throat or in the esophagus, weight loss, and progressive dysphagia symptoms. A questionnaire sent 3 years after the primary visit concerned the present symptoms. To investigate whether dysphagia could have been early symptom of malignancy, we surveyed the Finnish Cancer Registry database until the end of 2012.

Results: Most diagnoses remained descriptive: unspecific dysphagia (167, 55%). Five (0.02%) had malignant disease, for all of whom the suspicion of malignancy was evident. Finnish Cancer Registry data indicated that unspecific dysphagia did not develop into malignancy during a 3-year follow-up. Returned questionnaires numbered 154 (62%), of which 30 (19%) were asymptomatic patients; relieved symptoms in 36 (23%), fluctuating or unchanged symptoms in 43 (28%), and worse symptoms in 12 (8%). The remaining patients (33, 21%) had not answered that question or the answer was uninterpretable.

Conclusion: Further investigations to reveal malignancy seemed unnecessary if alarming clinical signs or findings were lacking. After 3 years, almost half the patients were asymptomatic or had milder symptoms revealing the condition's potential for spontaneous recovery.

Level Of Evidence: N/A. Laryngoscope, 126:2073-2078, 2016.
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http://dx.doi.org/10.1002/lary.25823DOI Listing
September 2016

Voice quality after treatment of early vocal cord cancer: a randomized trial comparing laser surgery with radiation therapy.

Int J Radiat Oncol Biol Phys 2014 Oct;90(2):255-60

Department of Oncology, Helsinki University Central Hospital, and University of Helsinki, Helsinki, Finland.

Objective: Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial.

Methods And Materials: Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO2 laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living.

Results: Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization.

Conclusions: Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.
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http://dx.doi.org/10.1016/j.ijrobp.2014.06.032DOI Listing
October 2014

Low expression of nuclear Toll-like receptor 4 in laryngeal papillomas transforming into squamous cell carcinoma.

Otolaryngol Head Neck Surg 2014 Nov 9;151(5):785-90. Epub 2014 Sep 9.

Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Objective: The malignant transformation rate of recurrent respiratory papillomatosis (RRP), a disease caused by human papillomavirus (HPV), has varied significantly. Cells of the human immune system express toll-like receptors (TLRs) that recognize particles from viruses and bacteria; TLRs are also present on tumor cells, and down-regulation of TLRs has been shown during the progression of HPV-associated neoplasia. The aim of this study was to determine the malignant transformation rate of laryngeal papillomas (LPs) and analyze the potential of TLR2, TLR4, and TLR9 immunoexpression as indicators of the increased cancer risk.

Study Design: Retrospective case-control study.

Setting: Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Subjects And Methods: We reviewed all patients with RRP treated for LPs between 1975 and 2011. Data from the Finnish Cancer Registry confirmed the number of patients diagnosed with laryngeal squamous cell carcinoma (LSCC). Laryngeal tissue specimens from patients developing LSCC were subjected to TLR2, TLR4, and TLR9 immunohistochemistry. Nine patients with RRP without malignant transformation and 19 patients with LSCC without a pre-existing LP served as controls.

Results: Nine of 324 patients (2.8%) with RRP developed LSCC. The intensity of nuclear staining of TLR4 was significantly lower in LPs transforming into LSCC than in LPs without malignant transformation. The expression of cytoplasmic TLR4 in LSCC correlated with tumor grade and T stage. Cytoplasmic TLR9 expression was significantly lower in LPs than in LSCC.

Conclusion: The expression of TLR4 may serve as a predictive marker of malignant transformation in LPs. High immunoexpression of cytoplasmic TLR4 in LSCC was associated with a more aggressive disease.
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http://dx.doi.org/10.1177/0194599814549730DOI Listing
November 2014

Laryngeal cancer in Finland: A 5-year follow-up study of 366 patients.

Head Neck 2016 Jan 27;38(1):36-43. Epub 2015 Jan 27.

Department of Otorhinolaryngology, Head and Neck Surgery, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.

Background: The purpose of this study was to acquire nationwide data on the management and outcome of laryngeal squamous cell carcinoma (SCC) in Finnish university hospitals over a 5-year posttreatment follow-up.

Methods: All records of patients diagnosed and treated for primary laryngeal SCC during 2001 to 2005 were reviewed.

Results: Three hundred sixty-six patients with laryngeal cancer were identified, 360 of whom had laryngeal SCC. Three hundred forty-two patients with laryngeal SCC (95%) were treated with curative intent. Five-year disease-specific survival (DSS) for T1a, T1b, T2, T3, and T4 glottic SCC was 100%, 95%, 78%, 79%, and 53%, respectively. The corresponding figures for T1 to T4 supraglottic SCC were 68%, 54%, 72%, and 59%.

Conclusion: Results of this nationwide study give a general overview of the outcome of unselected patients treated with unified guidelines. Patients with T2 tumors, usually treated with radiotherapy (RT), had a worse prognosis than expected. This patient group warrants further investigation and possibly treatment intensification.
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http://dx.doi.org/10.1002/hed.23834DOI Listing
January 2016

Detection of TS polyomavirus DNA in tonsillar tissues of children and adults: evidence for site of viral latency.

J Clin Virol 2014 Jan 27;59(1):55-8. Epub 2013 Nov 27.

Department of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Virology and Immunology, Helsinki University Central Hospital Laboratory Division, Helsinki, Finland.

Background: The trichodysplasia spinulosa-associated polyomavirus (TSPyV), a recently discovered species of the family Polyomaviridae, is associated with development of trichodysplasia spinulosa (TS), a rare follicular skin disease of immunocompromised individuals. The viral seroprevalence in the general population is ∼70%, with little known of its route of transmission, latency, or primary infection site.

Objectives: We aimed to determine whether the viral DNA is detectable in tonsillar tissue of constitutionally healthy individuals, and what the corresponding antiviral seroreactivities are.

Study Design: We tested 229 matched pairs of tonsillar tissue biopsies and serum samples from asymptomatic donors for TSPyV DNA by real-time quantitative PCR with primer pairs and Taq-Man probes targeting the VP1 and LT genes. The sera were studied by enzyme immunoassay (EIA) for TSPyV-VP1-IgG and the PCR-positive individuals also for -IgM and -IgG-avidity.

Results: TSPyV DNA was detectable in 8 (3.5%) of 229 tonsillar tissues, and in none of the corresponding sera. TSPyV IgG seroprevalence among children was 39% and among adults 70%. Each of the 8 PCR-positive subjects had antiviral IgG of high avidity but not IgM.

Conclusions: TSPyV PCR positivity of tonsillar samples of individuals with long-term immunity provides the first evidence of TSPyV in tonsils and suggests lymphoid tissue as a latency site of this emerging human pathogen.
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http://dx.doi.org/10.1016/j.jcv.2013.11.008DOI Listing
January 2014
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